Substance dependence as defined by the WHO is “A state, psychic and sometimes also physical, resulting from the interaction between a living organism and a drug, characterized by behavioural and other responses that always include a compulsion to take the drug on a continuous or periodic basis in order to experience its psychic effects, and sometimes to avoid the discomfort of its absence.”. That is, substance dependence can be divided into psychic dependence and physical dependence. In psychic dependence, there appears a strong desire “craving” for taking a certain substance, and in physical dependence, withdrawal symptoms appear upon interruption of dosing. A dependence-producing substance may also produce tolerance in those who take it, thus causing an increase in intake thereof. In the withdrawal syndrome, craving for a large amount of a substance is brought about due to extreme suffering, thus falling in a vicious cycle to make impossible to keep away from the substance. This vicious cycle constitutes substance dependence.
Substances causing substance dependence include stimulants (amphetamine, methamphetamine, MDMA), opioids (morphine, heroin), barbiturate type anesthetics, hallucinogens (LSD), cocaine, hemp (marijuana), cannabis, benzodiazepine type compounds (sedatives, hypnotics, anxiolytics), alcohol, and volatile organic solvents. Some stimulant substances have an appetite-suppressing effect and are thus used sometimes for dieting. It is also noted that some stimulant substances are mixed in “diet pills”. These drugs are those regarded as most important for measures against drug abuse in Japan because of the hazardous nature and prevalence thereof. Various problems with substance dependence are not only medical problems but also serious social problems.
If drug abuse is repeated, psychopathic symptom is increasingly experienced as chronic effect. Frequently found symptom examples include hyperacusia by which ambient sounds are heard louder than actual sounds and auditory hallucinations by which voices are heard in one's head, together with the noise of an air conditioner and the sound of running water, or voices coming from nowhere are heard without relation to such noise or sound. Such voices may be voices of his family, friends, acquaintances in some cases or completely unfamiliar voices in other cases and are heard to be accusatory, threatening, mandatory or interfering. If his life or inner thoughts are guessed rightly by the voices, he believes that a device such as a bugging device has been set somewhere, and will seek for it under the roof or floor or will disassemble electrical utility equipments. Inextricably linked to such false feeling, he comes to have a suspicion of being soiled by someone and harbors suspicion against his family and friends or becomes paranoid. Everywhere he goes, he has the idea of being chased by a person (for example, a policeman, a mafia member etc.) or has a visual hallucination that he saw that person lurking in the shadows. Such hallucinations and delusions resemble those of schizophrenia. There are also cases where the subtleties of emotion, or willingness, are attenuated through drug abuse for a prolonged period, and hallucinations and delusions in such cases may be hardly discriminated from those of schizophrenia.
The problem of psychopathic symptom caused by substance abuse lies in long-term persistence after chronic abuse, and in relapse due to alcohol drinking, sleeplessness, extreme stress etc. The former is called sequelae of substance abuse and the latter is called flashback phenomenon. Such pathology lasting long even after abstinence from substance use are obstacles for people who wish to recover from substance dependence, and this is another fear of substance abuse.
Therapy of substance dependence at present is initiated by abstaining from its causative substance, and substance therapy has been regarded as having little effect. If a sleeping pill or tranquilizer is administered without careful consideration, abuse of, or dependence on, such a prescription drugs may be caused, and in fact it is said that there are many patients with abuse of prescription drugs in addition to stimulant abuse.
As prior arts relating to therapeutic agents for substance dependence, Patent Document 1 discloses azabicyclo derivatives or benzoic acid derivatives (5-HT antagonist); Patent Document 2 discloses rolipram (phosphodiesterase inhibitor); Patent Document 3 discloses ifenprodil; Patent Document 4 discloses an inhibitor of degradation of an endogenous neuropeptidyl opioid; and Japanese Patent 5 discloses prophylaxis/therapy of substance dependence caused by dopamine autoreceptor agonists etc., as well as alleviation/prophylaxis of withdrawal syndrome. However, any of these therapeutic agents for substance dependence cannot be said to be satisfactory in their effect and are still not put to practical use.    Patent Document 1: Japanese Patent No. 2765845    Patent Document 2: JP-A1-HO 9-221423    Patent Document 3: JP-A1-H 11-29476    Patent Document 4: Pamphlet of International Publication WO89/03211    Patent Document 5: Western Germany Patent Application (Laid-Open) No. 3930282